Triggered activity is repetitive activity of cardia fibers that arises from afterdepolarizations. It is unrelated to any demonstrable circus movement and therefore, by definition, not reentrant, and never arises spontaneously (i.e., an action potential always is required to initiate it). In this study we propose to investigate systematically triggered activity resulting from delayed afterdepolarizations to (a) identify its similarities to and differences from 3 other arrhythmogenic mechanisms, reentry, abnormal automaticity (i.e., that which occurs at low levels of membrane potential and is not as readily overdrive suppressed as normal automaticity) and early afterdepolarizations, (b) develop "guidelines" that might relate the cellular electrophysiologic characteristics of such triggered activity to the body surface ECG and (c) test these guidelines in specific clinical arrhythmias. The hypothesis to be tested is that delayed afterdepolarizations do cause specific cardiac arrhythmias and that these can be differentiated from rhythms resulting from reentry, abnormal automaticity and early afterdepolarizations. We will test our hypothesis by studying isolated cardiac tissues, whole animal models and patient ECG's. For the first two groups, microelectrodes and intact animal electrophysiologic techniques will be used, for the third group, retrospective ECG analysis will be performed. The purpose of this subdivision is to permit us (1) to identify at the cellular level the electrophysiologic characteristics of triggered activity and its similarities to and differences from abnormal automaticity and reentry, (2) to test in intact animal models of ventricular arrhythmias our abilities to discriminate which mechanism is causing the arrythmia, and (3) based on 1 and 2 to develop guidelines that we can apply to arrhythmias in patients, with a view towards better identifying the mechanisms for them. The significance of the planned studies is that they will identify the electrophysiologic characteristics of the cellular mechanisms for arrhythmias including their response to pacing and to pharmacologic agents and therefore will permit the formulation of guidelines by which clinical arrhythmias can be tested. As a result, we should obtain an improved definition of the mechanisms for specific arrhythmias and more rigorous guidelines for their diagnosis and treatment than presently are available.